PMID- 27533909
OWN - NLM
STAT- MEDLINE
DCOM- 20170703
LR  - 20220331
IS  - 2163-0763 (Electronic)
IS  - 2163-0755 (Print)
IS  - 2163-0755 (Linking)
VI  - 81
IP  - 6
DP  - 2016 Dec
TI  - Unfractionated heparin after TBI reduces in vivo cerebrovascular inflammation, 
      brain edema and accelerates cognitive recovery.
PG  - 1088-1094
AB  - BACKGROUND: Severe traumatic brain injury (TBI) may increase the risk of venous 
      thromboembolic complications; however, early prevention with heparinoids is often 
      withheld for its anticoagulant effect. New evidence suggests low molecular weight 
      heparin reduces cerebral edema and improves neurological recovery after stroke 
      and TBI, through blunting of cerebral leukocyte (LEU) recruitment. It remains 
      unknown if unfractionated heparin (UFH) similarly affects brain inflammation and 
      neurological recovery post-TBI. We hypothesized that UFH after TBI reduces 
      cerebral edema by reducing LEU-mediated inflammation and improves neurological 
      recovery. METHODS: CD1 male mice underwent either TBI by controlled cortical 
      impact (CCI) or sham craniotomy. UFH (75 U/kg or 225 U/kg) or vehicle (VEH, 0.9% 
      saline) was administered 2, 11, 20, 27, and 34 hours after TBI. At 48 hours, pial 
      intravital microscopy through a craniotomy was used to visualize live brain LEUs 
      interacting with endothelium and microvascular fluorescein isothiocyanate-albumin 
      leakage. Neurologic function (Garcia Neurological Test, GNT) and body weight loss 
      ratios were evaluated 24 and 48 hours after TBI. Cerebral and lung wet-to-dry 
      ratios were evaluated post mortem. ANOVA with Bonferroni correction was used to 
      determine significance (p < 0.05). RESULTS: Compared to positive controls (CCI), 
      both UFH doses reduced post-TBI in vivo LEU rolling on endothelium, concurrent 
      cerebrovascular albumin leakage, and ipsilateral cerebral water content after 
      TBI. Additionally, only low dose UFH (75 U/kg) improved GNT at both 24 and 48 
      hours after TBI. High dose UFH (225 U/kg) significantly increased body weight 
      loss above sham at 48 hours. Differences in lung water content and blood pressure 
      between groups were not significant. CONCLUSIONS: UFH after TBI reduces LEU 
      recruitment, microvascular permeability, and brain edema to injured brain. Lower 
      UFH doses concurrently improve neurological recovery whereas higher UFH may 
      worsen functional recovery. Further study is needed to determine if this is 
      caused by increased bleeding from injured brain with higher UFH doses.
FAU - Nagata, Katsuhiro
AU  - Nagata K
AD  - From the Division of Traumatology, Surgical Critical Care & Emergency Surgery 
      (K.N., J.S-P., J.L.P.) and Department of Neurosurgery, Center for Brain Injury 
      and Repair (K.D.B., J.C., V.E.J., D.H.S., J.L.P.), University of Pennsylvania 
      Perelman School of Medicine, Philadelphia, Pennsylvania; Sidney Kimmel Medical 
      College at Thomas Jefferson University (J.M.), Philadelphia, Pennsylvania; 
      Department of Neurosurgery (S.L.), Qianfoshan Hospital, Shandong University, 
      Jinan, China; and Department of Emergency and Critical Care Medicine (K.K.), 
      Tokyo Medical University Hachioji Medical Center, Tokyo, Japan.
FAU - Kumasaka, Kenichiro
AU  - Kumasaka K
FAU - Browne, Kevin D
AU  - Browne KD
FAU - Li, Shengjie
AU  - Li S
FAU - St-Pierre, Jesse
AU  - St-Pierre J
FAU - Cognetti, John
AU  - Cognetti J
FAU - Marks, Joshua
AU  - Marks J
FAU - Johnson, Victoria E
AU  - Johnson VE
FAU - Smith, Douglas H
AU  - Smith DH
FAU - Pascual, Jose L
AU  - Pascual JL
LA  - eng
GR  - R01 NS092398/NS/NINDS NIH HHS/United States
GR  - R01 NS094003/NS/NINDS NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Trauma Acute Care Surg
JT  - The journal of trauma and acute care surgery
JID - 101570622
RN  - 0 (Anticoagulants)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/*therapeutic use
MH  - Brain Edema/etiology/*prevention & control/psychology
MH  - Brain Injuries, Traumatic/complications/psychology/*therapy
MH  - Capillary Permeability
MH  - Cognition
MH  - Disease Models, Animal
MH  - Heparin/*therapeutic use
MH  - Leukocyte Rolling
MH  - Male
MH  - Mice
PMC - PMC5367050
MID - NIHMS852860
COIS- DISCLOSURE The authors declare no conflicts of interest.
EDAT- 2016/08/18 06:00
MHDA- 2017/07/04 06:00
PMCR- 2017/12/01
CRDT- 2016/08/18 06:00
PHST- 2016/08/18 06:00 [pubmed]
PHST- 2017/07/04 06:00 [medline]
PHST- 2016/08/18 06:00 [entrez]
PHST- 2017/12/01 00:00 [pmc-release]
AID - 10.1097/TA.0000000000001215 [doi]
PST - ppublish
SO  - J Trauma Acute Care Surg. 2016 Dec;81(6):1088-1094. doi: 
      10.1097/TA.0000000000001215.